Thymocytes bearing T cell receptors (TCRs) that engage MHC self-peptide complexes with intermediate affinity are expanded in the thymus in a process called positive selection, whereas a subset that expresses high affinity receptors for self-peptides are eliminated through a process called negative selection. There is evidence that distinct TCR-linked signaling pathways culminate in these alternate fates. Engagement of the TCR by positive selecting ligands transmits calcineurin-dependent signals and activates the extracellular signal-regulated protein kinase (ERK) (Alberola-Ila J et al., 1995, Nature 373:620-3; Backstrom B T et al., 1998, Science 281:835-8; Werlen G et al., 2000, Nature 406:422-6; Delgado P et al., 2000, Nature 406:426-30; Hailman E et al., 2002, Immunity 16:839-48; Neilson J R et al., 2004, Immunity 20:255-66). In contrast, negative selection may depend on the action of Bim, a BH3—only proapoptotic Bcl-2 family member, which provokes downstream signals through Bax and Bak leading to cell death (Bouillet P et al., 2002, Nature 415:922-6; Strasser A et al., 2003, Immunol Rev 193:82-92). Although Jun kinase (JNK) has also been implicated in a TCR-signaling pathway that can lead to thymocyte apoptosis, the early signaling events that lead to negative selection have not previously been identified (Rincon M et al., 1998, J Exp Med 188:1817-30).